When humans go into space, they do not travel alone. They take their microbes with them—and science is just beginning to reveal how spaceflight affects the vast microbial communities that live in and on human bodies, known as the microbiome. In April, as part of its twins study, NASA reported how astronaut Scott Kelly’s microbiome changed during his marathon stay on the International Space Station (ISS). Now scientists who worked on that study have published new research that shows consistent impacts of low-Earth orbit on the gut bacteria of mice that traveled on other missions onboard the ISS and space shuttle. The mice’s microbiome responded to spaceflight similarly to Kelly’s.

The microbiome plays a complex role in human health and metabolism. Since the Human Microbiome Project launched in 2007, scientists have found that gut bacteria have far-reaching impacts on immunity, mental health and—in an area that is crucial to astronauts—bone-density regulation (astronauts can lose as much as 2 percent of bone density on average for every month in space). Understanding how the microbiome behaves during space travel is therefore an important part of preparing astronauts for long-term missions to Mars and beyond, says study co-author Fred Turek, a circadian biologist at Northwestern University co-author of the study.

In the paper, published last month in Microbiome, scientists found that the changes seen in the mouse microbiome on separate missions were similar to one another, and the team began to home in on what aspects of spaceflight were causing them. Northwestern systems biologist Peng Jiang, the study’s lead author, developed a new tool for analyzing microbiome data from multiple experiments, which allowed him and his colleagues to compare results from mice that were on the ISS in 2014 with data from those that traveled onboard the space shuttle three years prior. In each experiment, the animals were kept in cages specially designed for space travel and fed consistent diets. Researchers collected fecal samples and sequenced the genomes of the microbes inside. Jiang says he and his colleagues incorporated information about the abundance and diversity of different species, genera and other taxa of bacteria in their analysis.

In both missions—on the shuttle Atlantis’sfinal mission in 2011 and on the ISS’s first Rodent Research mission in 2014—the mouse microbiome’s community structure shifted, and the ratio of Firmicutes to Bacteroidetes, two bacterial phyla that together make up more than 90 percent of gut microbes, increased. During his year in space, Kelly’s microbiome underwent a similar shift, then returned to normal after he got back to Earth. Previous microbiome studies in humans and mice have linked elevated Firmicutes-to-Bacteroidetes ratios with dietary changes, obesity and human aging. In the new paper, the microbes experienced changes in their metabolism, turning on genes involved in fermentation and turning off genes involved in respiration. The implications of these changes for long-term space missions remain unclear.

To find out what might be causing the changes, Jiang and his colleagues compared data from the mouse studies conducted onboard the ISS and shuttle missions with results from experiments conducted on Earth. In the latter, researchers exposed mice to high doses of radiation to mimic its effects on their microbes during far-flung space missions. In the new study, the researchers saw different microbiome shifts than those observed in the Earth-based radiation experiments. They think this result was because the mice on the ISS and shuttle missions were still within the protective part of the magnetosphere—the region of charged particles trapped by Earth’s magnetic field—that shields our planet from cosmic radiation, called the Van Allen belt. “The type and extent of radiation exposure on [the] ISS is not likely to be similar to that in deep-space missions,” says Georgetown University systems biologist Amrita Cheema, who co-authored one of the Earth-based radiation studies but was not involved in the new paper. Cheema says more research is needed to determine what effect radiation could have on astronaut microbiomes on more distant missions. Martha Vitaterna, a geneticist at Northwestern, who co-authored the Microbiome study, agrees. “Just because we don’t see something that looks like radiation in low-Earth orbit doesn’t mean it’s not a worry,” she says.

Vitaterna says the stress of being in microgravity for extended periods was the most likely cause of the microbiome shifts observed in the mice on the ISS and shuttle. “If it’s not radiation, then the next thing you obviously would suspect is microgravity,” she says. Jamie Foster, an astrobiologist at the University of Florida, who was not involved in the study, agrees. “We’ve always had gravity through the four and a half billion years that this planet has been evolving,” she says. “Something is causing the shift in this population, and I wouldn’t be surprised if it was the stress of suddenly being in this really novel microgravity environment.” Does that mean that microbes in the gut are experiencing microgravity and responding to it directly? Or is microgravity causing a stress response in the mice that has a cascading effect on their microbes? It could be a bit of both. “Microgravity can have an effect on microbes’ physiology and even their gene expression,” Foster says. It could be that the microbes are physiologically experiencing something themselves or that they’re responding to a change in the mouse, she adds.

Teasing apart that question and others about how microbiomes will fare when humans travel to deep space will be the focus of continued research. Vitaterna says she and her colleagues are analyzing data from mice that recently spent more than two months on the ISS. The researchers, she asserts, will be able to ask questions such as: How quickly does the microbiome change? And does it continue to change throughout the duration of the space flight? “We can start to think about ‘How do we extrapolate that to longer-duration missions?’” Vitaterna says.